Oestrogen metabolism in lymphangioleiomyomatosis: catechol-O-methyltransferase pathway is not involved
- Benoit Paquettea,
- Pierre-Karl Fortiera,c,
- Julie Hérouxa,c,
- Paul A Thibodeaua,
- Richard Wagnera,
- Jiankang Liub,
- André Cantinc
- aDepartment of Radiobiology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4, bDivision of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720, USA, cDepartment of Medicine, Centre Universitaire de Santé de l'Estrie, Sherbrooke, Québec, Canada J1H 5N4
- Dr A Cantin email:
- Received 25 October 1999
- Revision requested 12 January 2000
- Revised 9 March 2000
- Accepted 17 March 2000
BACKGROUND Lymphangioleiomyomatosis (LAM) is an uncommon lung disease for which no effective method of treatment has been found. The predilection of LAM for premenopausal women has led to the assumption that hormonal factors play an important role in the pathogenesis of this disease. The aim of this study was to determine if women with LAM manifest alterations in the catechol-O-methyltransferase (COMT) pathway which is essential for preventing the generation of oestrogen derived reactive oxygen species (ROS).
METHODS Blood samples were collected from 15 women with LAM and compared with appropriate controls. The distribution of high and low activity alleles of COMT was determined with a PCR based RFLP assay. The enzymatic activity of COMT was measured in each sample and the potential presence of a circulating inhibitor of COMT was determined. Since an alteration in the COMT pathway could increase the oxidative stress, the plasma concentration of malondialdehyde (MDA), a secondary product generated from lipid peroxidation, has been used as an internal marker.
RESULTS The distribution of high and low activity alleles of COMT (namedCOMT HH,COMT LL, andCOMT HL) was similar in the two groups with proportions of 40%, 7%, and 53%, respectively, in the women with LAM and 38%, 6%, and 56% in the control subjects. The mean (SD) COMT activity was 24.2 (12.3) pmol/min/mg protein in women with LAM and 24.1 (6.3) pmol/min/mg protein in the control group. Incubation of plasma from women in the two groups with a preparation of commercial COMT showed that no detectable COMT inhibitor was present. The plasma concentration of MDA in the women with LAM was also not significantly different from control subjects.
CONCLUSIONS This study shows that there are no significant alterations in the COMT pathway of women with LAM. It is therefore unlikely that alterations in oestrogen mediated cell signalling pathways are mediated by oxidants derived from an excess of catecholoestrogens in LAM.